Kenneth J. McCormick

Biochemical Properties of a Defective Hamster C-Type Oncornavirus

A noninfectious hamster C-type oncornavirus (D9) associated with a spontaneous hamster lymphoma was characterized. The defective virions contained 70S RNA and the base composition was similar to that of a murine sarcoma-leukemia virus. With both endogenous and added templates, the virions were found to be deficient in DNA polymerase activity. These results suggest that DNA polymerase may be required for D9 infectivity.

Rheumatoid factor positive plasma and humoral cytotoxicity to malignant melanoma

Complement dependent cytotoxicity to malignant melanoma tumor cells was demonstrated in incubations that included rheumatoid factor (RF) positive plasma and normal plasma. Cytotoxicity was not demonstrated to cells from a number of normal tissues. The phenomenon involved coating of tumor cells with immunoglobulins and complement fixation. The activity in RF positive plasma was present in high titer and may not be RF. The activity in normal plasma was present in low titer, was found in plasma from eight out of 11 healthy subjects and may be a naturally occurring antibody. This previously undescribed humoral cytotoxicity system may participate in tumor host interactions, especially after therapy, when the majority of patients become RF seropositive.

Induction of Hepatomas in Hamsters by an Avian Adenovirus (CELO)

Summary Hepatomas were induced in approximately 4% of inbred LSH/LAK hamsters inoculated subcutaneously with CELO virus. The sera from these animals stained the CELO T antigen found in lytically infected chick kidney cells. The tumors contained hamster types A and C virus particles. The relationship between these indigenous hamster viruses and tumor induction by CELO virus is being investigated.

Hemagglutinating properties of CELO, an oncogenic avian adenovirus.

Chicken-embryo-lethal-orphan (CELO) virus, Phelps strain, agglutinated erythrocytes at 37 C. The hemagglutinating activity, which is a function of complete and incomplete virus particles, was sensitive to heat but not to pH. The soluble components of the virus were similar in sedimentation characteristics to those obtained from human adenovirus type 1. The effects of chemical and physical agents on CELO hemagglutinin, CELO infectivity, and red-cell receptors suggested that the last were protein in nature and that cell-virus attachment was mediated by amino groups on the virion. The attachment of virus to red blood cells via the penton projection was demonstrated by electron microscopy.

Chicken Embryo Lethal Orphan (CELO) Virus DNA Present in Hamster Cell Lines Derived from CELO-Induced Hepatomas

The kinetics of renaturation of the isolated DNA fragments of chicken embryo lethal orphan (CELO) virus generated by the restriction enzyme EcoR1 was measured in the presence of DNA extracted from two lines of CELO virus-induced hamster hepatoma cells and from control hamster cells. One hepatoma cell line (CILT-2), which did not produce the CELO virus tumor (T) antigen, lacked sequences from about one-half the virus genome while the other hepatoma cell line (CEHEP), which did produce the CELO virus T antigen, lacked sequences corresponding to one-fifth of the viral genome.

A Plaque Assay for Chick-Embryo-Lethal-Orphan (CELO) Virus

Summary A procedure was described for plaquing of avian adenovirus (CELO) in chick kidney cells. The media consisted of Eagles MEM with 2.5% fetal calf serum, 0.22% sodium bicarbonate and 0.04% protamine sulfate, in 1% Bacto agar. Using this medium, monolayers of chick kidney cells could easily be maintained for at least 12 days. Plaques could be counted on the 11th day, after addition of neutral red (0.04%) on the 10th day. An adsorption period of 3 hr at 3 7° gave optimal plaque counts.

Studies on an Oncogenic Avian Adenovirus (CELO) I. Biophysical Characterization

Summary CELO virus, from infected allantoic fluids, was treated with 1.0% sodium deoxycholate and 0.01% trypsin and centri-fuged to equilibrium in a rubidium chloride gradient. Two bands, at densities of approximately 1.34 and 1.29 g/cm3, were consistently found. Plaque titrations indicated that the band at 1.34 g/cm3contained the majority of infectious virus. Both hemagglutinating and CF activities were associated with these bands; however, soluble CF antigens were also present in the less dense regions of the gradients. The infectivity of purified CELO virions was heat stable and the virions did not contain the adenovirus group antigen.

Prevention of primary simian adenovirus type 7 (SA7) tumors in hamsters by adoptive transfer of lymphoid cells: role of different cell types.

Malignant neoplasms in general acquire neo-antigens, usually called tumor-specific transplantation antigen (TSTA). Chemically induced tumors usually exhibit antigens unique to each tumor, whereas tumors induced by a virus share a common antigen specific for that virus regardless of the histological type of tumor or host species in which the tumor was induced (1–3). These TSTA invoke an immune response, mainly of cell-mediated type. The immune control or progressive growth of the tumor depends upon many factors including strength of the cellular immune response (degree of sensitization of lymphoid cells), “sneaking through” or appearance of serum blocking factor (1, 3–5), and suppressor cells (6–8). It has generally been accepted that thymus-dependent lymphocytes (T) are primarily responsible for rejection of tumors (9–15). There is considerable evidence that macrophages also contribute an important effector mechanism against tumors (16). Recently, natural killer (NK) cells are also thought to be involved in tumor surveillance (17–19). Most of the studies of effector mechanisms of tumor immunity have been carried out in vitro, using various cytotoxicity assays. To assess the role of in vivo cell-mediated immune responses in tumor immunity, two main approaches usually have been used. One consisted of studying the influence of immuno-suppression (x-irradiation, thymectomy, anti-lymphocyte serum) on the development of tumors (20–24). The alternate approach is to augment cellular immune responses either through non-specific stimulation such as Bacillus Calmette-Guerin (BCG), Corynebacterium parvum (CP), poly I:C, etc. (25–28), or through adoptive transfer of specifically sensitized lymphoid cells (29–31).

Transplantation Resistance to Adenovirus-Induced Hepatocellular Carcinomas

Summary Two transplantable hepatic carcinomas of the hamster contained CELO virus-induced TSTA, confirming the etiological role of this avian adenovirus in the induction of hepatic tumors. Transplantation resistance could not be induced with oncogenic adenoviruses of human, simian, or canine origin.